Clinical evaluation of hepatic arterial infusion of low dose-CDDP and 5-FU with hyperthermotherapy: a preliminary study for liver metastases from esophageal and gastric cancer.

BACKGROUND/AIMS: The prognosis for gastric and esophageal cancer patients with liver metastases remains very poor. In most cases, liver metastasis is unresectable because of its number, size and location and therefore, other approaches need to be considered. METHODOLOGY: In this study we examined 4 patients. We showed the therapeutic benefits of employing hepatic arterial infusion of low-dose CDDP and 5-FU combined with hyperthermia for the treatment of liver metastases of gastric and esophageal cancer. RESULTS: All patients showed partial response, and bone marrow toxicities and gastrointestinal toxicities were extremely slight while liver toxicities were not observed at all. Moreover, 3 of the patients excluding patient 3 who had metastatic lesions other than liver metastases have still been alive for more than 17 months (17-28 months) maintaining a good quality of life. CONCLUSIONS: Therefore, it is suggested that the merits of both low dose-FP and hepatic arterial infusion chemotherapy contribute to ideal clinical effects, and that hyperthermotherapy could enhance clinical responses without potentiating any toxicities. However, this is just a preliminary study, and therefore, a prospective randomized control study is necessary to evaluate the efficiency of this therapy.

Clinical usefulness of an ATP heat sensitivity test using endoscopic biopsy materials from esophageal cancer patients.

The usefulness of a heat sensitivity test which involved performing an ATP assay on endoscopic biopsy materials for predicting the clinical response to hyperthermia was investigated in esophageal cancer patients. Following in vitro heat treatment of FM3A tumor cells, the heat sensitivity detected by ATPA was significantly correlated with that in the colony-forming assay, and the percent inhibition of the ATP level in the tumor cells was correlated with in vivo tumor growth. The heat sensitivity of the biopsy materials evaluated by ATPA correlated well with that of the resected specimens in 18 esophageal cancer patients, while the clinical response to thermal therapy was well predicted by the heat sensitivity of the biopsy materials evaluated by ATPA in seven of the patients. These results indicate that the heat sensitivity test conducted by performing an ATPA on endoscopic biopsy materials could be a useful indicator for predicting the clinical response to thermal therapy.

Treatment of chronic granulocytic leukemia in the accelerated phase by transfusion of autologous buffy-coat cells--a case report.

We treated a patient with chronic granulocytic leukemia (CGL), in the accelerated phase by intensive chemotherapy followed by the infusion of cryopreserved peripheral blood buffy-coat cells. The cells had been stored for 32 months. The chemotherapy consisted of daunorubicin 40 mg X 2 days, vincristine 2 mg X 1 day, cytosine arabinoside (Ara-C) 200 mg X 6 days and prednisolone 30 mg X 7 days in the first week, then Ara-C 3 g/m2 X 3 days and cyclophosphamide 60 mg/kg X 2 days in the second week, but reversion to the chronic phase was not achieved. Therefore, total body irradiation (TBI) was added to repeated intensive chemotherapy followed by infusion of the remaining cells. Marrow recovery was good. The patient is currently alive and has been in the chronic phase for 22 months. This preliminary result indicates that this therapy may be tried soon after transformation in CGL and that TBI is an important part of therapy in BMT in the accelerated or blastic phase of CGL.

[Experimental and clinical studies on chemosensitivity tests of anticancer agents by human tumor clonogenic assay].

In vitro chemosensitivity tests of anticancer agents for 119 fresh human tumors were performed by the human tumor clonogenic assay (HTCA) technique and the following results were obtained. Colony growth (greater than or equal to 5 colonies/dish) was observed in 35 of 50 gastric cancers (70.0%), 10 of 17 colon cancers (58.8%), 13 of 14 breast cancers (92.9%), two of six esophageal cancers (33.3%), three of six sarcomas (50.0%), three of 16 hematological malignancies (18.8%) and seven of 10 other tumors (70.0%). Colony growth rate differed according to the type of tumor. Fifty four tumors formed adequate colony growth (greater than or equal to 30 colonies/dish) for the chemosensitivity test. Mitomycin C (MMC), 5-Fluorouracil (5-FU), 4-hydroperoxy cyclophosphamide (CPM), Adriamycin (ADM), Cis-dichlorodiammineplatinum (CDDP), and alpha-interferon (IFN-alpha) were tested. The average positive rates of MMC, 5-FU, CPM, CDDP, and IFN-alpha were 26.9, 21.6, 10.5, 26.9, 36.8, and 23.3% respectively for all the tumors tested. In gastric cancer, the positive rates of MMC and 5-FU were 24.0 and 21.6% respectively, whereas the rates were 33.3 and 33.3% in colon cancer and 18.2 and 16.7% in breast cancer respectively. Each tumor exhibited its own chemosensitivity rates against various anticancer agents. Eighteen of the results obtained were comparable to clinical responses. The true positive rate was 50.0% (2/4) and the true negative rate 92.9% (13/14). A statistically significant correlation was observed between the results of HTCA and clinical responses (chi 2 test, p less than 0.05). The combined effects of IFN-alpha and MMC were surveyed against 20 gastroenterological tumors. Nine tumors exhibited synergistic effect, though antagonistic effect was observed in three tumors. The effects of oxygen tension (2%, 5%, 20%) on colony growth were investigated. The greatest development of colonies occurred at an oxygen of five percent, which is considered to be physiological oxygen tension, and statistically significant increases of plating efficiencies at 5% O2 as compared to those at 20% O2 were observed (t-test, p less than 0.025).

[Clinical studies on a rapid screening assay for anticancer agents with nude mice and isotopic evaluation].

A rapid method using nude mice has been established as an in vivo model for assessing the chemosensitivity of individual human tumors, in which the final evaluation is made with 3H-thymidine (3H-TdR) incorporation into the treated tumor. In 234 of 289 cancers, the chemosensitivity of anticancer agents was evaluated by this method. This assay proved to be feasible in a sufficiently high percentage of human primary tumors (81.0%). The rate of positive sensitivity against all tumors was 23.8% for MMC, 12.3% for 5-FU, 29.1% for CPM and 23.5% for ADM, respectively. The sensitivity of anticancer agents varied according to the type of cancer. Correlation between the sensitivity test and the end results after chemotherapy in cases of inoperable gastrointestinal cancers was investigated, prospectively. Out of 19 cases, the 50% survival time of 11 patients treated with sensitive agents was longer than that of 8 patients treated with insensitive agents. From a prospective-correlative study carried out on 25 patients, this assay appeared to be correlated with clinical response (overall agreement, 76.0%) with specific agreements of sensitivity and resistance of 37.5% and 94.1%, respectively. From these results, it seems reasonable to conclude that this sensitivity test using a human/nude mouse system is a useful screening assay for revealing appropriate agents for the treatment of patients with cancer.

[Comparison of human tumor clonogenic and nude mouse-isotope assays in anticancer-agent sensitivity tests].

Comparative studies between the in vitro human tumor clonogenic assay (HTCA) and our original in vivo method (NM-IA) in which the final evaluation was made with 3H-TdR incorporation of tumor cells transplanted into nude mice were simultaneously performed on 44 fresh human solid tumors (22 gastric cancers, 6 breast cancers, 4 gall bladder cancers, 4 liposarcomas and 8 other tumors). Mitomycin C (MMC), 5-fluorouracil (5-FU), adriamycin (ADM) and cyclophosphamide (CPM) were tested. The evaluable rate was 73% (32/44) in HTCA and 89% (38/44) in NM-IA. Although correlation between the results of HTCA and those of MN-IA was obtained for MMC and ADM, no correlation was observed for 5-FU and CPM.